Multiple myeloma

Definition

By Mayo Clinic staff

Multiple myeloma is a cancer of your plasma cells. Plasma cells are a type of white blood cell present in your bone marrow.

In multiple myeloma, a group of abnormal plasma cells (myeloma cells) multiplies, raising the number of plasma cells to a more than normal level. The result can be erosion of your bones. The disease also interferes with the function of your bone marrow and immune system, which can lead to anemia and infection. Multiple myeloma may also cause kidney problems.

The disease is called multiple myeloma because myeloma cells can occur in multiple bone marrow sites in your body.

If you have multiple myeloma but don't have symptoms, your doctors may just monitor your condition. If you're experiencing symptoms, various treatments are available.

Symptoms

By Mayo Clinic staff

Although multiple myeloma may not cause symptoms early in the disease, it's likely that you'll experience signs and symptoms as the disease progresses.

Signs and symptoms of the disease can vary from person to person. Common multiple myeloma symptoms include:

• Bone pain.
• Presence of abnormal proteins — which can be produced by myeloma cells — in your blood or urine. These proteins — which are antibodies or parts of antibodies — are called monoclonal, or M, proteins. Often discovered during a routine exam, monoclonal proteins may indicate multiple myeloma, but also can indicate other conditions.
• High level of calcium in your blood. This can occur when calcium from affected bones dissolves into your blood.

If you have a high calcium level in your blood, you may experience signs and symptoms such as:

• Excessive thirst and urination
• Constipation
• Nausea
• Loss of appetite
• Mental confusion

Anemia can occur as myeloma cells replace oxygen-carrying red blood cells in your bone marrow, which may lead to another common symptom — fatigue.

Other signs and symptoms of multiple myeloma may include:

• Bone pain, particularly in your back or ribs
• Unexplained bone fractures
• Repeated infections — such as pneumonia, bladder or kidney infection, or sinusitis
• Weight loss
• Weakness or numbness in your legs

Causes

By Mayo Clinic staff

Multiple myeloma

(The growth of myeloma cells (bluish-stained cells) inhibits the growth of normal bone marrow cells.)

Although the exact cause isn't known, doctors do know that multiple myeloma begins with one abnormal plasma cell in your bone marrow — the soft, blood-producing tissue that fills in the center of most of your bones. This abnormal cell then starts to multiply.

Because abnormal cells don't mature and then die as normal cells do, they accumulate, eventually overwhelming the production of healthy cells. Healthy bone marrow consists of a small number of plasma cells, less than 5 percent. But in people with multiple myeloma, the number of plasma cells often increases to more than 10 percent.

Because myeloma cells may circulate in low numbers in your blood, they can populate other bone marrow sites in your body, even far from where they began. Uncontrolled plasma cell growth can damage bones and surrounding tissue. It can also interfere with your immune system's ability to fight infections by inhibiting your body's production of normal antibodies.

Researchers investigating cause
Experts aren't sure why this process begins. But, researchers are studying the DNA of plasma cells to try to understand what changes occur that cause these cells to become cancer cells. Though they haven't yet discovered the cause of these changes, they have found some common abnormalities in myeloma cells. For example, many myeloma cells are missing all or part of one chromosome — chromosome 13. Cells with a missing or defective chromosome 13 tend to be more aggressive and harder to treat than are cells with a normal chromosome 13.

A connection with MGUS
Multiple myeloma sometimes develops from a condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS is more common in adults over age 50. This condition, like multiple myeloma, is marked by the presence of M proteins — produced by abnormal plasma cells — in your blood. However, in MGUS, the amount of the abnormal proteins isn't high enough to cause harm, and no damage to the bones occurs.

Risk factors

By Mayo Clinic staff

Multiple myeloma isn't contagious. Most people who develop multiple myeloma have no clearly identifiable risk factors for the disease.

Some factors that may increase your risk of multiple myeloma include:

• Age. The majority of people who develop multiple myeloma are older than 50, with most diagnosed around age 70. Few cases occur in people younger than 40.
• Sex. Men are more likely to develop the disease than are women.
• Race. Blacks are about twice as likely to develop multiple myeloma as are whites.
• History of a monoclonal gammopathy of undetermined significance. Every year 1 percent of the people with MGUS in the United States develop multiple myeloma.
• Obesity. Your risk of multiple myeloma is increased if you're overweight or obese.

Other factors that may increase your risk of developing multiple myeloma include exposure to radiation and working in petroleum-related industries.

When to seek medical advice

By Mayo Clinic staff

If you're persistently more tired than you used to be, you've lost weight, and you experience bone pain, repeated infections, loss of appetite, excessive thirst and urination, persistent nausea, increased constipation, or weakness or numbness in your legs, your signs and symptoms may indicate multiple myeloma or other serious diseases. See your doctor to determine the underlying cause.

Tests and diagnosis

By Mayo Clinic staff

Your doctor may first detect signs of multiple myeloma before you ever have symptoms — through blood and urine tests conducted during a routine physical exam. If you don't yet have symptoms, these lab tests may be repeated every few months so that your doctor can track whether your disease is progressing and determine the best time to start treatment.

Blood and urine tests
A blood test called serum protein electrophoresis separates your blood proteins and can detect the presence of M proteins, called an "M spike," in your blood. Parts of M proteins may also be detected in a test of your urine — when found in urine, they're referred to as Bence Jones proteins.

If your doctor discovers M proteins, you'll likely need additional blood tests to measure blood cell counts and levels of calcium, uric acid and creatinine. Your doctor may also conduct other blood tests to check for beta2-microglobulin — another protein produced by myeloma cells — or to measure the percent of plasma cells in your bone marrow.

Other tests
You may also need other tests. They may include:

• Imaging. X-rays of your skeleton can show whether your bones have any thinned-out areas, common in multiple myeloma. If a closer view of your bones is necessary, your doctor may use magnetic resonance imaging (MRI) or computerized tomography (CT) scanning.
• Bone marrow examination. Your doctor may also conduct a bone marrow examination by using a needle to remove a small sample of bone marrow tissue. The sample is then examined under a microscope to check for myeloma cells.

Staging and classification
These tests can help confirm whether you have multiple myeloma or another condition. If tests indicate you have multiple myeloma, the results from these tests allow your doctor to classify your disease as stage 1, stage 2 or stage 3. People with stage 3 myeloma are more likely to have one or more signs of advanced disease, including greater numbers of myeloma cells and kidney failure.

Complications

By Mayo Clinic staff

Multiple myeloma can result in several complications:

• Impaired immunity. Myeloma cells inhibit the production of antibodies needed for normal immunity. Having multiple myeloma may make you more likely to develop infections, such as pneumonia, sinusitis, bladder or kidney infection, skin infections and shingles.
• Bone problems. Multiple myeloma also can affect your bones, leading to erosion of bone mass and fractures. The condition may cause compression of your spinal cord. Signs of this medical emergency include weakness, or even paralysis, in your legs.
• Impaired kidney function. Multiple myeloma may cause problems with kidney function, including kidney failure. Higher calcium levels in the blood related to eroding bones can interfere with your kidneys' ability to filter your blood's waste. The proteins produced by the myeloma cells can cause similar problems, especially if you become dehydrated.
• Anemia. As cancerous cells crowd out normal blood cells, multiple myeloma can also cause anemia and other blood problems.

Treatments and drugs

By Mayo Clinic staff

Generally, if you have multiple myeloma and aren't experiencing symptoms, you don't need treatment. However, your doctors will likely monitor your condition at variable intervals, checking for signs — such as increasing levels of M protein in your blood or urine — that indicate the disease is progressing. If it is, you may need treatment to help prevent symptoms. In people diagnosed with asymptomatic multiple myeloma, the risk of developing symptoms is about 10 percent a year for the first five years after learning that they have the disease.

If you're experiencing symptoms, treatment can help relieve pain, control complications of the disease, stabilize your condition and slow the progress of the disease.

Standard treatments for myeloma
Though there's no cure for multiple myeloma, with good treatment results you can usually return to near-normal activity. The appropriate multiple myeloma treatment depends on your needs, medical status and general health. You may also wish to consider approved clinical trials as an option.

Standard treatment options include:

• Chemotherapy. Chemotherapy involves using medicines — taken orally as a pill or given through an intravenous (IV) injection — to kill myeloma cells. Chemotherapy is often given in cycles over a period of months, followed by a rest period. Often chemotherapy is discontinued during what is called a plateau phase or remission, during which your M protein level remains stable. You may need chemotherapy again if your M protein level begins to rise. Common chemotherapy drugs used to treat myeloma are melphalan (Alkeran), cyclophosphamide (Cytoxan), vincristine (Oncovin), doxorubicin (Adriamycin) and liposomal doxorubicin (Doxil).
• Corticosteroids. Corticosteroids such as prednisone and dexamethasone (Decadron) have been used for decades to treat multiple myeloma. They are typically given as pills. Some research suggests that high doses of steroids may not be needed, and that lower doses may be safer and more effective.
• Stem cell transplantation. This treatment involves using high-dose chemotherapy — usually high doses of melphalan — along with transfusion of previously collected immature blood cells (stem cells) to replace diseased or damaged marrow. The stem cells can come from you or from a donor, and they may be from either blood or bone marrow.
• Thalidomide (Thalomid). Thalidomide, a drug originally used as a sedative and to treat morning sickness in the 1950s, was removed from the market after it was found to cause severe birth defects. However, the drug received approval from the Food and Drug Administration (FDA) again in 1998, first as a treatment for skin lesions caused by leprosy. Thalidomide is currently FDA-approved in conjunction with the corticosteroid called dexamethasone for the treatment of newly diagnosed cases of multiple myeloma. This drug is given orally.
• Bortezomib (Velcade). Velcade was the first approved drug in a new class of medications called proteasome inhibitors. It is administered intravenously. It works by blocking the action of proteasomes, which causes cancer cells to die. One study showed that bortezomib had more than twice the response rate of a commonly used drug, dexamethasone. Bortezomib is approved for use as an initial treatment for people with multiple myeloma.
• Lenalidomide (Revlimid). Lenalidomide is chemically similar to thalidomide, but appears to be more potent and cause fewer side effects. It is given orally. Lenalidomide is FDA-approved for use in combination with dexamethasone as a treatment for people who have received at least one prior therapy for multiple myeloma.
• Radiation therapy. This treatment uses high-energy penetrating waves to damage myeloma cells and stop their growth. Radiation therapy may be used to target myeloma cells in a specific area — for instance, to more quickly shrink a tumor that's causing pain or destroying a bone.

Initial therapy for myeloma
The initial chemotherapy used to treat multiple myeloma depends on whether you're considered a candidate for stem cell transplantation. Factors such as the risk of your disease progressing, your age and your general health play a part in determining whether stem cell transplantation may be right for you.

• If you're considered a candidate for stem cell transplantation: Your initial therapy will likely exclude melphalan because this drug can have a toxic effect on stem cells, making it impossible to collect enough of them. You may begin treatment with the most common initial myeloma therapy in the United States, thalidomide plus dexamethasone. Or your doctor may instead recommend a newer regimen, lenalidomide plus low-dose dexamethasone.

  Your stem cells will likely be collected after you've undergone three to four months of treatment with these initial agents. Your doctor may recommend undergoing the stem cell transplant soon after your cells are collected or delaying the transplant until after a relapse, if it occurs. Your age and your personal preference are important factors that will help your doctor make his or her recommendation.

• If you're not considered a candidate for stem cell transplantation: Your initial therapy is likely to be a combination of melphalan, prednisone and thalidomide (MPT). If the side effects are intolerable, melphalan plus prednisone is another option (MP). This type of therapy is typically given for about 12 to 18 months.

Treatments for relapsed or treatment-resistant multiple myeloma
Most people who are treated for multiple myeloma eventually experience a relapse of the disease. And in some cases, none of the currently available, first-line therapies slow the cancer cells from multiplying. If you experience a relapse of multiple myeloma, your doctor may recommend repeating another course of the treatment that initially helped you. Another option is trying one or more of the other treatments typically used as first-line therapy, either alone or in combination.

Research on a number of promising new treatment options is ongoing, and these drugs offer important options for those with multiple myeloma. Talk to your doctor about what clinical trials may be available to you.

Treating complications
Because multiple myeloma can cause a number of complications, you may also need treatment for those specific conditions. For example:

• Back pain. Taking pain medication or wearing a back brace can help relieve the back pain you might experience with multiple myeloma.
• Kidney complications. People with severe kidney damage may need dialysis.
• Infections. Antibiotics may be necessary to help treat infections or to help reduce your risk of them.
• Bone loss. You may take medications called bisphosphonates, such as pamidronate (Aredia) or zoledronic acid (Zometa), which bind to the surface of your bones and help prevent bone loss. Treatment with these drugs is associated with the risk of harm to the jawbone. If you're taking these medications, don't have dental procedures done without consulting your doctor first.
• Anemia. If you have persistent anemia, your doctor may prescribe erythropoietin injections. Erythropoietin is a naturally occurring hormone made in the kidneys that stimulates the production of red blood cells. Research suggests that the use of erythropoietin may increase the risk of blood clots in some people with myeloma.

Lifestyle and home remedies

By Mayo Clinic staff

The following tips may help you keep multiple myeloma under control:

• Stay active. Exercise helps keep your bones stronger. If pain keeps you from being active, ask your doctor about ways to lessen the pain.
• Drink fluids. Drinking fluids can help keep you from becoming dehydrated. And by drinking plenty of fluids, you help dilute the Bence Jones protein fragments in your urine, which may help prevent kidney damage.
• Eat a balanced diet. One way to promote your overall health and cope with any form of cancer is to eat well. The amount of M protein in your system isn't affected by how much protein you eat, so there's no need to limit protein intake unless told otherwise by your doctor. Don't take vitamins, herbs or medications without your doctor's approval because they may interfere with your treatment.

Coping and support

By Mayo Clinic staff

A diagnosis of cancer can be extremely challenging. Remember that no matter what your concerns or prognosis, you're not alone. These strategies and resources may make dealing with cancer easier:

• Know what to expect. Find out everything you can about your cancer — the type, stage, risks, your treatment options and their side effects. The more you know, the more active you can be in your care. In addition to talking with your doctor, look for information in your local library and on the Internet. The National Cancer Institute will answer questions over the phone from the public at 800-4-CANCER, or 800-422-6237. Or contact the American Cancer Society at 800-ACS-2345, or -800-227-2345. Information is also available on their Web sites.
• Be proactive. Although you may feel tired and discouraged, don't let others — including your family or your doctor — make important decisions for you. It's vital that you take an active role in your treatment.
• Maintain a strong support system. Having a support system and a positive attitude can help you cope with any issues, pain and anxieties that might occur. Although friends and family can be your best allies, they sometimes may have trouble dealing with your illness. If so, the concern and understanding of a formal support group or others coping with cancer can be especially helpful. Although support groups aren't for everyone, they can be a good source for practical information for you and your family, too. You may also find you develop deep and lasting bonds with people who are going through the same things you are.
• Set reasonable goals. Having goals helps you feel in control and can give you a sense of purpose. But don't choose goals you can't possibly reach. You may not be able to work a 40-hour week, for example, but you may be able to work at least part time. In fact, many people find that continuing to work can be helpful.
• Take time for yourself. Eating well, relaxing and getting enough rest can help combat the stress and fatigue of cancer. Also, plan ahead for the downtimes, when you may need to rest more or limit what you do.
• Stay active. Having cancer doesn't mean you have to stop doing the things you enjoy or normally do. For the most part, if you feel well enough to do something, go ahead and do it. It's important to stay involved as much as you can.